ELA_RAT
ID ELA_RAT Reviewed; 54 AA.
AC P0DP76;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Apelin receptor early endogenous ligand {ECO:0000250|UniProtKB:P0DMC3};
DE AltName: Full=Protein Elabela {ECO:0000250|UniProtKB:P0DMC2};
DE Short=ELA {ECO:0000250|UniProtKB:P0DMC2};
DE AltName: Full=Protein Toddler {ECO:0000250|UniProtKB:P0DMC2};
DE Flags: Precursor;
GN Name=Apela {ECO:0000250|UniProtKB:P0DMC3}; Synonyms=Ela, Tdl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RG Genoscope - CEA;
RL Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=26611206; DOI=10.1007/s00395-015-0521-6;
RA Perjes A., Kilpioe T., Ulvila J., Magga J., Alakoski T., Szabo Z.,
RA Vainio L., Halmetoja E., Vuolteenaho O., Petaejae-Repo U., Szokodi I.,
RA Kerkelae R.;
RT "Characterization of apela, a novel endogenous ligand of apelin receptor,
RT in the adult heart.";
RL Basic Res. Cardiol. 111:2-2(2016).
RN [4]
RP FUNCTION.
RX PubMed=28137936; DOI=10.1161/circulationaha.116.023218;
RA Yang P., Read C., Kuc R.E., Buonincontri G., Southwood M., Torella R.,
RA Upton P.D., Crosby A., Sawiak S.J., Carpenter T.A., Glen R.C.,
RA Morrell N.W., Maguire J.J., Davenport A.P.;
RT "Elabela/Toddler is an endogenous agonist of the apelin APJ receptor in the
RT adult cardiovascular system, and exogenous administration of the peptide
RT compensates for the downregulation of its expression in pulmonary arterial
RT hypertension.";
RL Circulation 135:1160-1173(2017).
CC -!- FUNCTION: Endogenous ligand for the apelin receptor (APLNR)
CC (PubMed:28137936). Hormone required for mesendodermal differentiation,
CC blood vessels formation and heart morphogenesis during early
CC development and for adult cardiovascular homeostasis (PubMed:26611206,
CC PubMed:28137936). Drives internalization of APLNR. Acts as a motogen by
CC promoting mesendodermal cell migration during gastrulation by binding
CC and activating APLNR. Acts as an early embryonic regulator of cellular
CC movement with a role in migration and development of cardiac progenitor
CC cells. May act as a chemoattractant for the activation of angioblast
CC migration toward the embryonic midline, i.e. the position of the future
CC vessel formation, during vasculogenesis. Positively regulates sinus
CC venosus (SV)-derived endothelial cells migration into the developing
CC heart to promote coronary blood vessel sprouting. Plays a role in
CC placental vascular development; promotes placental trophoblast invasion
CC and spiral artery remodeling in the uterus (By similarity). Involved in
CC the regulation of maternal cardiovascular homeostasis to prevent
CC gestational hypertension and for potent cardioprotective functions
CC during heart failure (PubMed:26611206). Mediates myocardial
CC contractility in an ERK1/2-dependent manner (PubMed:26611206).
CC {ECO:0000250|UniProtKB:P0DMC2, ECO:0000250|UniProtKB:P0DMC3,
CC ECO:0000250|UniProtKB:P0DMC4, ECO:0000269|PubMed:26611206,
CC ECO:0000269|PubMed:28137936}.
CC -!- SUBUNIT: Interacts with APLNR. {ECO:0000250|UniProtKB:P0DMC3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0DMC4}.
CC Secreted, extracellular space {ECO:0000250|UniProtKB:P0DMC4}.
CC Note=Found in blood plasma. Found in serum of pregnant mice, peaking at
CC midgestation; indicating a maternal and zygotic origin of circulating
CC APELA during pregnancy. {ECO:0000250|UniProtKB:P0DMC3,
CC ECO:0000250|UniProtKB:P0DMC4}.
CC -!- SIMILARITY: Belongs to the Elabela/Toddler family. {ECO:0000305}.
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DR EMBL; AABR07025051; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FQ214304; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; XP_008770257.1; XM_008772035.2.
DR AlphaFoldDB; P0DP76; -.
DR SMR; P0DP76; -.
DR Ensembl; ENSRNOT00000107155; ENSRNOP00000082744; ENSRNOG00000067022.
DR GeneTree; ENSGT00950000183499; -.
DR PRO; PR:P0DP76; -.
DR Proteomes; UP000002494; Chromosome 16.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0031704; F:apelin receptor binding; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0007512; P:adult heart development; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0060183; P:apelin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0035050; P:embryonic heart tube development; ISS:UniProtKB.
DR GO; GO:0007509; P:mesoderm migration involved in gastrulation; ISS:UniProtKB.
DR GO; GO:0060674; P:placenta blood vessel development; ISS:UniProtKB.
DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0045823; P:positive regulation of heart contraction; IMP:UniProtKB.
DR GO; GO:1901165; P:positive regulation of trophoblast cell migration; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
PE 3: Inferred from homology;
KW Angiogenesis; Developmental protein; Differentiation; Gastrulation;
KW Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000250|UniProtKB:P0DMC3"
FT CHAIN 26..54
FT /note="Apelin receptor early endogenous ligand"
FT /id="PRO_0000441047"
SQ SEQUENCE 54 AA; 6823 MW; CFE4FC06026B0360 CRC64;
MRFQPLFWVF FIFAMSLLFI TEEKSVNFPR RRKLYRHNCF RRRCISLHSR VPFP
